The broad based pathogenesis study described here accomplishes all of the AREA program objectives: (1) supporting meritorious research, (2) exposing undergraduates to research, and (3) strengthening the research environments in non-research intensive schools. The experimental model, Bordetella avium, causes a highly contagious respiratory disease in its avian hosts, primarily turkeys, with striking similarity to whooping cough in children, caused by B. pertussis. Species specificity is determined largely by the attachment process of the bacteria to the tracheal cilia of the relevant host, and pathogenic effects are limited to the upper respiratory tract of the bird. Using genetic and biochemical approaches and in vivo and in vitro models, we and our collaborators have identified 19 genes important in virulence, including those encoding surface molecules (Fha, fimbrae, and LPS). In addition, we discovered two proteins essential for hemagglutination that are different from the hemagglutinin of B. pertussis. In the proposed study we will use classic methods to purify and characterize these factors while continuing to define and explore the constellation of virulence factors of this organism. We will also broaden our studies by developing tissue and/or organ culture models for studying toxicity, an area that is largely unexplored for B. avium. The systematic examination of virulence factors in B. avium will yield important and useful information about that organism and the disease in turkeys, and may prove helpful in understanding disease causation among all the Bordetella species. Over the 3 year project period, this project will expose more than 60 students in laboratory and independent research to an excellent model of research and give them an opportunity to make unique contributions to the study of an important pathogen. Having a broad based approach provides students with numerous opportunities to explore relevant scientific questions, exert creative thinking, and learn the fundamentals of biomedical research. The ongoing collaborative study has served a catalytic role over the last eight years, increasing the interest of students and faculty alike in research, and will continue to enhance the research environment for undergraduates in the sciences at Drew University.